The study results provide initial clinical evidence of hematologic, cytogenetic and molecular anti-cancer activity of AP24534 in heavily pretreated patients with resistant and refractory chronic myeloid leukemia (CML), including those with the T315I mutant variant of the target protein, Bcr-Abl. An abstract describing these data is being submitted for presentation at a major hematology meeting to be held later this year.

Treatment of CML or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) with Bcr-Abl inhibitors is effective in most patients but frequently results in the emergence of Bcr-Abl mutations that confer drug resistance over time. The T315I mutant of Bcr-Abl currently accounts for approximately 15 to 20 percent of all drug-resistant cases of CML and Ph+ ALL.

First-generation therapies, such as imatinib (Gleevec®), and second-generation therapies, such as dasatinib (Sprycel®) and nilotinib (Tasigna®), are not able to inhibit this mutated protein and, therefore, are not effective against all forms of CML and Ph+ ALL.

Clinical Proof-of Concept in Patients with CML and Ph+ ALL.

Thirty-two patients have been enrolled to date in this trial in six dosing groups (once daily oral dosing) at five medical centers in the United States; 28 of the patients have resistant and refractory CML or Ph+ ALL. All patients have previously been treated with the currently available first- and second-generation targeted therapies for CML and in most instances, other investigational agents as well.

The patients with CML and Ph+ALL enrolled in this study only had very limited treatment options available to them: stem cell transplants, conventional palliative chemotherapy or investigational agents. The study commenced patient enrollment in the second quarter of 2008 and will continue enrolling patients until approximately 50 patients have been enrolled. Dose-escalation will continue until dose-limiting toxicity is observed.

Key preliminary findings to date include:

In patients with a variety of Bcr-Abl mutations, hematologic responses, cytogenetic responses, and molecular responses have been observed with AP24534 treatment. Hematologic and cytogenetic responses have also been seen in patients with the T315I mutation, which is resistant to all approved Bcr-Abl inhibitors. Collectively, these data suggest a significant degree of anti-tumor activity of AP24534 in highly resistant CML patients.

In addition, of 23 CML patients in the four highest dosing groups, 19 patients remain on study without disease progression, evidence of control of their disease. Most importantly, of 12 CML patients with the T315I mutation, nine patients remain on study without disease progression, providing further evidence of control of their disease.

For many of the patients in the highest dosing groups, the duration of treatment with AP24534 has been relatively short. In these patients, it is still early for complete-response assessment. Even in spite of this, evidence of significant improvement in multiple blood-cell lineages has been observed.

Preliminary safety assessment shows that AP24534 is well tolerated without dose-limiting toxicity at doses studied to date. The most common drug-related adverse events have been thrombocytopenia (low platelet count) and neutropenia (low white blood cell count), which the Company believes reflects the underlying disease and the extensive pre-treatment of the patients in the trial.

To date, pharmacokinetic data indicate that blood levels predicted preclinically to be associated with complete inhibition of Bcr-Abl mutations have been surpassed. Pharmacodynamic data show evidence that AP24534 is acting mechanistically as designed.

“Especially given that we have not yet reached a maximally tolerated dose, we believe that these preliminary results provide promising evidence of clinical proof-of-concept of AP24534 in patients with drug-resistant and refractory CML and Ph+ ALL, including those with the T315I mutation,” said Frank G. Haluska, M.D., Ph.D., vice president, clinical affairs at ARIAD.

Huntsman Cancer Institute (HCI) at the University of Utah (U of U) has been selected to participate in the Beat AML Master Trial, an innovative clinical trial sponsored by The Leukemia & Lymphoma Society (LLS). The clinical trial is testing several new targeted therapies for the treatment of patients with acute myeloid leukemia (AML). HCI is the only facility in the Mountain West offering this trial to AML patients.

The heart is the first organ to develop in the womb and the first cause of concern for many parents. Parents and doctors often have to consider the mother's health as well as the potential risk regarding how medication could affect their baby."We can try to rebuild the shape of the early development heart in the lab," said Professor Zhen Ma. "It mimics the very early stage, during the embryo genesis - how the heart was formed."